Sodium Bicarbonate → (5)-tert-butyl 2-(3-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)prop-1-enyl)-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate

HRID 1471625Notes

Reaction equation

HRID 1471625 reaction equation
[CH2:1]([C:4]1[CH:5]=[C:6]([CH2:10][C@H:11]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:12]([N:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH3:15])=[O:13])[CH:7]=[CH:8][CH:9]=1)[CH:2]=[CH2:3].Br[C:33]1[N:34]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C:35]2[C:40]([C:41]=1[CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=2.C(=O)(O)[O-].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([O:26][C:25]([NH:24][C@H:11]([C:12]([N:14]([C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:15])=[O:13])[CH2:10][C:6]1[CH:5]=[C:4]([CH2:1][CH:2]=[CH:3][C:33]2[N:34]([C:48]([O:50][C:51]([CH3:52])([CH3:54])[CH3:53])=[O:49])[C:35]3[C:40]([C:41]=2[CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:9]=[CH:8][CH:7]=1)=[O:31])([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 90281421tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylateHCID 125500528(5)-Tert-butyl 3-(3-allylphenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 90281387(5)-tert-butyl 2-(3-(3-(2-(tert-butoxycarbonylamino)-3-((4-methoxyphenyl)(methyl)amino)-3-oxopropyl)phenyl)prop-1-enyl)-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylateYield 48.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A suspension of (5)-tert-butyl 3-(3-allylphenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (220 mg, 0.52 mmol), tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate (297 mg, 0.78 mmol), sodium bicarbonate (435 mg, 5.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.05 mmol) in 4 ml of DMF was heated to 125° C. overnight. The reaction was cooled to room temperature and then filtered through celite. The filtrate was concentrated and the crude product was introduced to a silica gel loading column and purified by column chromatography (30-60% EtOAc/Hexans) to provide the desired product (178 mg, 0.25 mmol), 47%. MS (m/z) 726 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered through celite
  3. concentrationThe filtrate was concentrated
  4. additionthe crude product was introduced to a silica gel loading column
  5. custompurified by column chromatography (30-60% EtOAc/Hexans)

Sources & evidence

ORD record
ord-cea81b9df22747b69aa7e030f466c771
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

Loading…